Effect of okadaic acid on immunologic and non-immunologic histamine release in rat mast cells

We have studied the effect of the protein phosphatase (PP) inhibitor, okadaic acid (OKA) on histamine release elicited by immunologic and non-immunologic stimuli in peritoneal and pleural rat mast cells. When cells were stimulated with antigen (egg albumin), OKA strongly inhibited histamine release. This finding suggests that PP1 and PP2A substrates mediate immunoglobulin E-(IgE) dependent secretion in mast cells. In contrast, after non-immunologic activation of mast cells with different drugs, such as the neuropeptide growth hormone releasing factor (GRF) and the cytostatic agents Adriamycin, navelbine and mitoxantrone, there is no effect of OKA on histamine secretion. These results indicate that IgE-dependent secretion is mediated by substrates of PP1 and PP2A, whereas following non-immunological stimuli, they activate pathways that lead to protein phosphorylation; these proteins are not substrates of PP1 and PP2A.